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Pharmacogenetics of Clopidogrel in Acute Coronary Syndromes (PHARMCLO)

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ClinicalTrials.gov Identifier: NCT03347435
Recruitment Status : Terminated (Ethics Committe decision)
First Posted : November 20, 2017
Last Update Posted : November 20, 2017
Sponsor:
Information provided by (Responsible Party):
Diego Ardissino, Azienda Ospedaliero-Universitaria di Parma

Brief Summary:
The antiplatelet agent clopidogrel is an effective drug for the prevention of thrombotic events in patients with acute coronary syndromes, and is therefore one of the most frequently prescribed drugs worldwide. Accumulating data suggest that the response to clopidogrel is characterised by significant inter-patient variability in the degree of platelet inhibition and the risk of cardiovascular events. Recent research findings have highlighted the role of genetic variations in determining antiplatelet response variability, and this has aroused interest in genotyping all thienopyridine-eligible patients in order to identify those who would be at increased risk of harm if treated with clopidogrel. This is a prospective, multicentre, randomised study enrolling consecutive patients hospitalised because of an ACS with or without ST-segment elevation. The patients are randomised to undergo or not tests for CYP2C19*2, CYP2C19*17 and ABCB1 3435 genetic variants immediately after diagnosis. The genotyping is done using a Q3 System (a compact platform that enables the classic laboratory analysis of DNA by means of real-time PCR). The Q3 has been designed as a low entry-cost, portable, point-of-care instrument for foolproof use by unskilled personnel. The patients randomised to the pharmacogenomic arm receive one of the ADP receptor antagonists (clopidogrel/prasugrel/ticagrelor) on the basis of an algorithm that consider genetic and clinical variables. The patients randomised to the standard treatment arm receive clopidogrel or prasugrel or ticagrelor on the basis of the standard of care (clinical algorithm alone). For each patient, a record is made of the occurrence of cardiovascular death, non-fatal MI, stroke, BARC-defined bleeding, and definite or probable stent thrombosis. The primary endpoint is the composite of death due to cardiovascular causes, non-fatal MI and stroke. The secondary endpoints is the occurrence of definite or probable stent thrombosis, and BARC-defined major bleeding events (types 3-5).

Condition or disease Intervention/treatment Phase
Acute Coronary Syndromes Genetic: genetic tests for CYP2C19*2, CYP2C19*17 and ABCB1 3435 Other: clinical algorithm Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 889 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacogenetics of Clopidogrel in Acute Coronary Syndromes
Study Start Date : June 2013
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Genotype/ phenotype guided group
The patients randomized to the genotype/phenotype guided group undergo genetic tests for CYP2C19*2, CYP2C19*17 and ABCB1 3435 genetic variants immediately after diagnosis of ACS and receive one of the ADP receptor antagonists (clopidogrel/prasugrel/ticagrelor) on the basis of an algorithm that consider genetic and clinical variables.
Genetic: genetic tests for CYP2C19*2, CYP2C19*17 and ABCB1 3435
The CYP2C19*2 (10q24.1-q24.3; rs4244285), CYP2C19*17 (10q24.1-q24.3; rs12248560) and ABCB1 3435 (7q21.1; rs1045642) genetic variants will be genotyped using an ST Q3 system. The conventional genotyping methods so far used for diagnostic purposes will not be used in this study because appropriate labs may not be readily available and the processing time is prohibitive. Q3 is a compact platform enabling the classical laboratory analysis of DNA by means of real-time PCR. The Q3 has been designed as a low entry-cost, portable, point-of-care instrument for foolproof use by unskilled personnel. Antiplatelet therapy will be choose on the basis of clinical and genetic algorithm.

Active Comparator: phenotype only guided group
The patients randomized to the phenotype only guided group receive clopidogrel or prasugrel or ticagrelor on the basis of the standard of care on the basis of clinical algorithm alone.
Other: clinical algorithm
Antiplatelet therapy will be choose on the basis of clinical algorithm alone




Primary Outcome Measures :
  1. Composite of cardiovascular death, non fatal myocardial infarction, stroke and BARC-defined major bleeding events 3 to 5. [ Time Frame: 12 months ]
    The primary endpoint will be the composite of cardiovascular death, non fatal myocardial infarction, stroke and BARC-defined major bleeding events 3 to 5 at 12 months follow-up.


Secondary Outcome Measures :
  1. occurrence of definite or probable stent thrombosis. [ Time Frame: 12 months ]
    The secondary endpoint variable will be the occurrence of definite or probable stent thrombosis at 12 months follow-up.

  2. cardiovascular death [ Time Frame: 12 months ]
    individual components of primary endpoint at 12 months follow-up

  3. non fatal myocardial infarction [ Time Frame: 12 months ]
    individual components of primary endpoint at 12 months follow-up

  4. stroke [ Time Frame: 12 months ]
    individual components of primary endpoint at 12 months follow-up

  5. BARC-defined major bleeding events 3 to 5 [ Time Frame: 12 months ]
    individual components of primary endpoint at 12 months follow-up



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of ACS (STE-ACS or NSTE-ACS) during the index hospitalisation
  • Age >18 years
  • Ability to sign the informed consent form
  • Ability to attend scheduled visits

Exclusion Criteria:

  • Cognitive or other causes of an inability to provide informed consent or follow study procedures
  • Any contraindication to the use of ADP P2Y12 inhibitors
  • Life expectancy <1 year
  • Thrombolytic therapy within the previous 24 hours
  • Known ABCB1, CYP2C19 *2 orCYP2C19 *17 genotype

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03347435


Locations
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Italy
Ospedale Ramazzini
Carpi, Modena, Italy, 41012
Ospedale di Vaio
Fidenza, Parma, Italy, 43036
Azienda Ospedaliero Universitaria di Parma
Parma, Italy, 43123
Ospedale Guglielmo da Saliceto
Piacenza, Italy, 29121
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria di Parma
Investigators
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Principal Investigator: Diego Ardissino, MD Azienda Ospedaliero-Universitaria di Parma

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Diego Ardissino, Director of Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma
ClinicalTrials.gov Identifier: NCT03347435     History of Changes
Other Study ID Numbers: 11210
First Posted: November 20, 2017    Key Record Dates
Last Update Posted: November 20, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Diego Ardissino, Azienda Ospedaliero-Universitaria di Parma:
clopidogrel
pharmacogenetics
antiplatelet therapy
acute coronary syndromes
Additional relevant MeSH terms:
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Acute Coronary Syndrome
Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Clopidogrel
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs